High Risk for Lopinavir Resistance After Sustained Treatment Failure

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Investigators found that most patients retained susceptibility to darunavir up to one year after failure and viral load increases were modest.
Investigators found that most patients retained susceptibility to darunavir up to one year after failure and viral load increases were modest.

Intermediate-/high-level lopinavir resistance develops in many people with HIV within 1 year when lopinavir/ritonavir is exposed to sustained viral load replication, according to results published in Clinical Infectious Diseases.

The results indicate that annual viral load testing, which is the current World Health Organization recommendation, would identify failure during a timeframe when most patients would still benefit from switching to darunavir.

The study included 2164 stored plasma samples from 386 participants who had been randomly assigned to protease inhibitor (PI) monotherapy (ritonavir-boosted lopinavir after initial PI plus raltegravir induction) in the EARNEST trial. The researchers tested the viral load of the plasma samples and performed protease genotypic resistance testing in samples with viral load >1000 copies/mL. They assessed the evolution of drug-resistant mutations from virologic failure (viral load >1000 copies/mL).

Overall, 107 participants experienced virologic failure, with 20% (n=21) having intermediate/high resistance to lopinavir. Of these, 26% (n=28) had at least 1 PI mutation.

At 40 to 48 weeks after treatment failure, 49 participants had intermediate-/high-level resistance to lopinavir, and 36 had resistance to atazanavir. Only 12 participants experienced resistance to darunavir, and only 1 participant had intermediate resistance.

The researchers found that at least 1 PI mutation developed in 73% of participants who experienced virologic failure. The most common PI mutations were M461, I54V, and V82A.

“In this study of [viral load] failure on lopinavir monotherapy, we found that patients often failed without PI mutations, but that resistance accumulated with longer time on the failing regimen,” the researchers wrote.

Reference

Thompson JA, Kityo C, Dunn D, et al. Evolution of protease inhibitor resistance in HIV-1-infected patients failing protease inhibitor monotherapy as second-line therapy in low-income countries: an observational analysis within the EARNEST randomised trial. [published online July 28, 2018]. Clin Infect Dis. doi:10.1093/cid/ciy589-

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